Heparin is a heterogeneous mixture of sulfated mucopolysaccharides of various molecular weights and a polyelectrolysis with a great concentration of negative charges spread over the surface of the molecule. As an anticoagulant cofactor, however, only 1/3 of the commercial heparin has been found to be biologically active. The half-life of heparin in vivo is short. Heparin also does not dissolve in organic solvents. We intend to study the relationship of the chemical structure of heparin to its bioactivity for its chemical modification. We propose to chemically utilize fractionated heparin in interrelated studies: 1. To synthesize a long-life heparin. 2. To increase heparin solubility in organic solvents by molecular modification of heparin. Prior to chemical modification of heparin, the heterogeneous commercial heparin will be fractionated into a series of homogenous fractions. The fractions will be characterized in terms of their anticoagulant activities. The fraction of highest anticoagulant activity will be used for chemical modifications.